tbuckley/cabot-search huggingface dataset:
Recent progress in application of nanovaccines for enhancing mucosal immune responses
Authors: Guangsheng Du, Ming Qin, Xun Sun
Journal: Acta Pharmaceutica Sinica B (2022)

Mucosal vaccines that stimulate both mucosal and systemic immune responses are desirable, as they could prevent the invading pathogens at their initial infection sites in a convenient and user-friendly way. Nanovaccines are receiving increasing attention for mucosal vaccination due to their merits in overcoming mucosal immune barriers and in enhancing immunogenicity of the encapsulated antigens. Herein, we summarized several nanovaccine strategies that have been reported for enhancing mucosal immune responses, including designing nanovaccines that have superior mucoadhesion and mucus penetration capacity, designing nanovaccines with better targeting efficiency to M cells or antigen-presenting cells, and co-delivering adjuvants by using nanovaccines. The reported applications of mucosal nanovaccines were also briefly discussed, including prevention of infectious diseases, and treatment of tumors and autoimmune diseases. Future research progresses in mucosal nanovaccines may promote the clinical translation and application of mucosal vaccines.
Heart Disease and Stroke Statistics—2015 Update
Authors: Dariush Mozaffarian, Emelia J. Benjamin, Alan S. Go, Donna K. Arnett, Michael J. Blaha, Mary Cushman, Sarah de Ferranti, Jean-Pierre Després, Heather J. Fullerton, Virginia J. Howard, Mark D. Huffman, Suzanne E. Judd, Brett M. Kissela, Daniel T. Lackland, Judith H. Lichtman, Lynda D. Lisabeth, Simin Liu, Rachel H. Mackey, David B. Matchar, Darren K. McGuire, Emile R. Mohler, Claudia S. Moy, Paul Muntner, Michael E. Mussolino, Khurram Nasir, Robert W. Neumar, Graham Nichol, Latha Palaniappan, Dilip K. Pandey, Mathew J. Reeves, Carlos J. Rodriguez, Paul D. Sorlie, Joel Stein, Amytis Towfighi, Tanya N. Turan, Salim S. Virani, Joshua Z. Willey, Daniel Woo, Robert W. Yeh, Melanie B. Turner
Journal: Circulation (2014)
Overview of Randomized Trials of Angiotensin-Converting Enzyme Inhibitors on Mortality and Morbidity in Patients With Heart Failure
Authors: Rekha Garg
Journal: JAMA (1995)

<h3>Objective.</h3> —To evaluate the effect of angiotensin-converting enzyme (ACE) inhibitors on mortality and morbidity in patients with symptomatic congestive heart failure. <h3>Data Sources and Study Selection.</h3> —Data were obtained for all completed, published or unpublished, randomized, placebo-controlled trials of ACE inhibitors that were at least 8 weeks in duration and had determined total mortality by intention to treat, regardless of sample size. Trials were identified based on literature review and correspondence with investigators and pharmaceutical firms. <h3>Data Extraction.</h3> —Using standard tables, data were extracted by one author and confirmed where necessary by the other author or the principal investigator of the trial. Unpublished data were obtained by direct correspondence with the principal investigator of each study or pharmaceutical firm. <h3>Data Synthesis.</h3> —The data for each outcome were combined using the Yusuf-Peto adaptation of the Mantel-Haenszel method. Overall, there was a statistically significant reduction in total mortality (odds ratio [OR], 0.77; 95% confidence interval [CI], 0.67 to 0.88;<i>P</i>&lt;.001) and in the combined endpoint of mortality or hospitalization for congestive heart failure (OR, 0.65; 95% CI, 0.57 to 0.74;<i>P</i>&lt;.001). Similar benefits were observed with several different ACE inhibitors, although the data were largely based on enalapril maleate, captopril, ramipril, quinapril hydrochloride, and lisinopril. Reductions for total mortality and the combined endpoint were similar for various subgroups examined (age, sex, etiology, and New York Heart Association class). However, patients with the lowest ejection fraction appeared to have the greatest benefit. The greatest effect was seen during the first 3 months, but additional benefit was observed during further treatment. The reduction in mortality was primarily due to fewer deaths from progressive heart failure (OR, 0.69; 95% CI, 0.58 to 0.83); point estimates for effects on sudden or presumed arrhythmic deaths (OR, 0.91; 95% CI, 0.73 to 1.12) and fatal myocardial infarction (OR, 0.82; 95% CI, 0.60 to 1.11) were less than 1 but were not significant. <h3>Conclusions.</h3> —Total mortality and hospitalization for congestive heart failure are significantly reduced by ACE inhibitors with consistent effects in a broad range of patients. (<i>JAMA</i>. 1995;273:1450-1456)
STUDIES ON THE CHEMICAL NATURE OF THE SUBSTANCE INDUCING TRANSFORMATION OF PNEUMOCOCCAL TYPES
Authors: Maclyn McCarty, Oswald T. Avery
Journal: The Journal of Experimental Medicine (1946)

It has been shown that extremely minute amounts of purified preparations of desoxyribonuclease are capable of bringing about the complete and irreversible inactivation of the transforming substance of Pneumococcus Type III. The significance of the effect of the enzyme, and its bearing on the chemical nature of the transforming substance, together with certain considerations concerning the biological specificity of desoxyribonucleic acids in general, are discussed.
Spore exines increase vitamin D clinical bioavailability by mucoadhesion and bile triggered release
Authors: Alberto Diego-Taboada, Thozhukat Sathyapalan, Fraser Courts, Mark Lorch, Farooq Almutairi, Benjamin P. Burke, Kate Harris, Martin Kruusmägi, Thomas Walther, Jonathan Booth, Andrew N. Boa, Stephen J. Archibald, Colin Thompson, Stephen L. Atkin, Grahame Mackenzie
Journal: Journal of Controlled Release (2022)
ERS scientific awards: striving for inclusivity
Authors: Maeve Tsu, Céline Genton, Sejal Saglani, Marc Humbert, Anita Simonds, Nicolas Roche, Christopher E. Brightling, Niki Ubags, Louise E. Donnelly
Journal: European Respiratory Journal (2022)

<b>Through the ERS scientific awards strategy, the selection and evaluation process continues to be refined to meet the needs of a more inclusive seeking era and reflect the diversity of the ERS membership</b> https://bit.ly/3agqb3H
Premature aging of the immune system affects the response to SARS-CoV-2 mRNA vaccine in β-thalassemia: role of an additional dose
Authors: Rita Carsetti, Chiara Agrati, Valeria Maria Pinto, Barbara Gianesin, Rita Gamberini, Monica Fortini, Susanna Barella, Rita Denotti, Silverio Perrotta, Maddalena Casale, Aurelio Maggio, Lorella Pitrolo, Eleonora Tartaglia, Eva Piano Mortari, Francesca Colavita, Vincenzo Puro, Massimo Francalancia, Valeria Marini, Marco Caminati, Filippo Mazzi, Lucia De Franceschi, Gian Luca Forni, Franco Locatelli
Journal: Blood (2022)
Natriuretic peptide pathways in heart failure: further therapeutic possibilities
Authors: S Jeson Sangaralingham, Michaela Kuhn, Valentina Cannone, Horng H Chen, John C Burnett
Journal: Cardiovascular Research (2022)

The discovery of the heart as an endocrine organ resulted in a remarkable recognition of the natriuretic peptide system (NPS). Specifically, research has established the production of atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) from the heart, which exert pleiotropic cardiovascular, endocrine, renal, and metabolic actions via the particulate guanylyl cyclase A receptor (GC-A) and the second messenger, cGMP. C-type natriuretic peptide (CNP) is produced in the endothelium and kidney and mediates important protective auto/paracrine actions via GC-B and cGMP. These actions, in part, participate in the efficacy of sacubitril/valsartan in heart failure (HF) due to the augmentation of the NPS. Here, we will review important insights into the biology of the NPS, the role of precision medicine, and focus on the phenotypes of human genetic variants of ANP and BNP in the general population and the relevance to HF. We will also provide an update of the existence of NP deficiency states, including in HF, which provide the rationale for further therapeutics for the NPS. Finally, we will review the field of peptide engineering and the development of novel designer NPs for the treatment of HF. Notably, the recent discovery of a first-in-class small molecule GC-A enhancer, which is orally deliverable, will be highlighted. These innovative designer NPs and small molecule possess enhanced and novel properties for the treatment of HF and cardiovascular diseases.
A CRISPR/Cas9 engineered MplS504N mouse model recapitulates human myelofibrosis
Authors: Fabienne R. S. Adriaanse, Jennifer L. Kamens, Peter Vogel, Sadie M. Sakurada, Shondra M. Pruett-Miller, Ronald W. Stam, C. Michel Zwaan, Tanja A. Gruber
Journal: Leukemia (2022)
Type 2 diabetes, gut microbiome, and systems biology: A novel perspective for a new era
Authors: Yoscelina Estrella Martínez-López, Diego A. Esquivel-Hernández, Jean Paul Sánchez-Castañeda, Daniel Neri-Rosario, Rodolfo Guardado-Mendoza, Osbaldo Resendis-Antonio
Journal: Gut Microbes (2022)

The association between the physio-pathological variables of type 2 diabetes (T2D) and gut microbiota composition suggests a new avenue to track the disease and improve the outcomes of pharmacological and non-pharmacological treatments. This enterprise requires new strategies to elucidate the metabolic disturbances occurring in the gut microbiome as the disease progresses. To this end, physiological knowledge and systems biology pave the way for characterizing microbiota and identifying strategies in a move toward healthy compositions. Here, we dissect the recent associations between gut microbiota and T2D. In addition, we discuss recent advances in how drugs, diet, and exercise modulate the microbiome to favor healthy stages. Finally, we present computational approaches for disentangling the metabolic activity underlying host-microbiota codependence. Altogether, we envision that the combination of physiology and computational modeling of microbiota metabolism will drive us to optimize the diagnosis and treatment of T2D patients in a personalized way.
Emerging epigenetic therapies of cardiac fibrosis and remodelling in heart failure: from basic mechanisms to early clinical development
Authors: Timothy A McKinsey, Roger Foo, Chukwuemeka George Anene-Nzelu, Joshua G Travers, Ronald J Vagnozzi, Natalie Weber, Thomas Thum
Journal: Cardiovascular Research (2022)

Cardiovascular diseases and specifically heart failure (HF) impact global health and impose a significant economic burden on society. Despite current advances in standard of care, the risks for death and readmission of HF patients remain unacceptably high and new therapeutic strategies to limit HF progression are highly sought. In disease settings, persistent mechanical or neurohormonal stress to the myocardium triggers maladaptive cardiac remodelling, which alters cardiac function and structure at both the molecular and cellular levels. The progression and magnitude of maladaptive cardiac remodelling ultimately leads to the development of HF. Classical therapies for HF are largely protein-based and mostly are targeted to ameliorate the dysregulation of neuroendocrine pathways and halt adverse remodelling. More recently, investigation of novel molecular targets and the application of cellular therapies, epigenetic modifications, and regulatory RNAs has uncovered promising new avenues to address HF. In this review, we summarize the current knowledge on novel cellular and epigenetic therapies and focus on two non-coding RNA-based strategies that reached the phase of early clinical development to counteract cardiac remodelling and HF. The current status of the development of translating those novel therapies to clinical practice, limitations, and future perspectives are additionally discussed.
A monkeypox virus infection mimicking primary syphilis
Authors: Martina Turco, Fabrizio R. Mancuso, Luigi Pisano
Journal: British Journal of Dermatology (2022)

Given the current monkeypox virus (MPXV) outbreak in at-risk men who have sex with men (MSM), clinicians should consider MPXV a differential diagnosis of syphilis, in any patient with a solitary painless genital nodule.
Reply
Authors: Alexander Queck, Michael Praktiknjo, Christian Jansen, Jonel Trebicka
Journal: Hepatology (2022)

We thank Luo et al. for the interest in our manuscript, although all answers to the raised concerns are found in the published manuscript. We agree that baseline liver function correlates with mortality, and we reported in detail no significant differences in baseline characteristics between groups; in particular, Model for End‐Stage Liver Disease, Child‐Pugh score, and age did not differ significantly, whereas albumin was higher in the groups with higher mortality (table 4). Moreover, Luo et al. stated that bilirubinemia >7 mg/dl is not a contraindication for transjugular intrahepatic portosystemic shunt (TIPS) insertion for ascites. This is a dangerous and misleading statement because studies so far have excluded those patients.1 There is evidence that bilirubin below 3 mg/dl is a good biomarker to predict outcome in patients with ascites.2 The strong association of bilirubin levels with post‐TIPS outcome reinforces the recommendation of guidelines for extreme caution for TIPS insertion for ascites if bilirubin >3–5 mg/dl.3,4 Although the quality of stents has improved over time, we included many patients and followed them over a long period of time. Indeed, we have reported the stent types used here (figure S7). Luo et al. raised an important issue of portal hepatic pressure gradient (PPG) variation and changes over time in our patients. It is very unlikely that in the real world outside of clinical trials longitudinal invasive measurements of PPG after TIPS are routinely performed. Ultrasound‐based assessment of patency is the routine follow‐up of choice. Therefore, we try to elaborate an easy‐to‐obtain surrogate marker at the time of TIPS insertion that is applicable for most cases in real‐life practice. Hereby, percentage decrease in PPG is a good marker for response to treatment in ascites control in our cohort. Finally, we agree that in recently compensated cases with ascites as the first decompensating event, the amount of ascites may be prognostic.5 However, all patients in our study received TIPS for therapy of recurrent and refractory ascites. Thus, the cited study does not apply to our patients and therefore the concern is unjustified. We thank again Luo et al. and hope that our answers could address their concerns and avoid confusion in further readers.
High HbA1c Levels Are Associated With Development of Trigger Finger in Type 1 and Type 2 Diabetes: An Observational Register-Based Study From Sweden
Authors: Mattias Rydberg, Malin Zimmerman, Anders Gottsäter, Katarina Eeg-Olofsson, Lars B. Dahlin
Journal: Diabetes Care (2022)

OBJECTIVE Trigger finger (TF) is a hand disorder causing the fingers to painfully lock in flexion. Diabetes is a known risk factor; however, whether strict glycemic control effectively lowers risk of TF is unknown. Our aim was to examine whether high HbA1c was associated with increased risk of TF among individuals with diabetes. RESEARCH DESIGN AND METHODS The Swedish National Diabetes Register (NDR) was cross-linked with the health care register of the Region of Skåne in southern Sweden. In total, 9,682 individuals with type 1 diabetes (T1D) and 85,755 individuals with type 2 diabetes (T2D) aged ≥18 years were included from 2004 to 2019. Associations between HbA1c and TF were calculated with sex-stratified, multivariate logistic regression models with 95% CIs, with adjustment for age, duration of diabetes, BMI, and systolic blood pressure. RESULTS In total, 486 women and 271 men with T1D and 1,143 women and 1,009 men with T2D were diagnosed with TF. Increased levels of HbA1c were associated with TF among individuals with T1D (women OR 1.26 [95% CI 1.1–1.4], P = 0.001, and men 1.4 [1.2–1.7], P &amp;lt; 0.001) and T2D (women 1.14 [95% CI 1.2–1.2], P &amp;lt; 0.001, and men 1.12 [95% CI 1.0–1.2], P = 0.003). CONCLUSIONS Hyperglycemia increases the risk of developing TF among individuals with T1D and T2D. Optimal treatment of diabetes seems to be of importance for prevention of diabetic hand complications such as TF.
Image-guided in situ cancer vaccination with combination of multi-functional nano-adjuvant and an irreversible electroporation technique
Authors: Jun-Hyeok Han, Yun Young Lee, Ha Eun Shin, Jieun Han, Jeon Min Kang, Chi-Pin James Wang, Jung-Hoon Park, Se-Na Kim, Jong-Hwi Yoon, Ho-Keun Kwon, Dae-Hwan Park, Tae-Eun Park, Young Bin Choy, Dong-Hyun Kim, Tae-Hyung Kim, Junhong Min, Ik-Hwan Kim, Chun Gwon Park, Dong Keun Han, Wooram Park
Journal: Biomaterials (2022)
Circulating Tumor DNA Identifies Diverse Landscape of Acquired Resistance to Anti–Epidermal Growth Factor Receptor Therapy in Metastatic Colorectal Cancer
Authors: James T. Topham, Chris J. O'Callaghan, Harriet Feilotter, Hagen F. Kennecke, Young S. Lee, Weimin Li, Kimberly C. Banks, Katie Quinn, Daniel J. Renouf, Derek J. Jonker, Dongsheng Tu, Eric X. Chen, Jonathan M. Loree
Journal: Journal of Clinical Oncology (2022)

Anti-epidermal growth factor receptor (EGFR) antibodies are effective treatments for metastatic colorectal cancer. Improved understanding of acquired resistance mechanisms may facilitate circulating tumor DNA (ctDNA) monitoring, anti-EGFR rechallenge, and combinatorial strategies to delay resistance.Patients with treatment-refractory metastatic colorectal cancer (n = 169) enrolled on the CO.26 trial had pre-anti-EGFR tissue whole-exome sequencing (WES) compared with baseline and week 8 ctDNA assessments with the GuardantOMNI assay. Acquired alterations were compared between patients with prior anti-EGFR therapy (n = 66) and those without. Anti-EGFR therapy occurred a median of 111 days before ctDNA assessment.ctDNA identified 12 genes with increased mutation frequency after anti-EGFR therapy, including EGFR (P = .0007), KRAS (P = .0017), LRP1B (P = .0046), ZNF217 (P = .0086), MAP2K1 (P = .018), PIK3CG (P = .018), BRAF (P = .048), and NRAS (P = .048). Acquired mutations appeared as multiple concurrent subclonal alterations, with most showing decay over time. Significant increases in copy-gain frequency were noted in 29 genes after anti-EGFR exposure, with notable alterations including EGFR (P < .0001), SMO (P < .0001), BRAF (P < .0001), MET (P = .0002), FLT3 (P = .0002), NOTCH4 (P = .0006), ERBB2 (P = .004), and FGFR1 (P = .006). Copy gains appeared stable without decay 8 weeks later. There were 13 gene fusions noted among 11 patients, all but one of which was associated with prior anti-EGFR therapy. Polyclonal resistance was common with acquisition of ≥ 10 resistance related alterations noted in 21% of patients with previous anti-EGFR therapy compared with 5% in those without (P = .010). Although tumor mutation burden (TMB) did not differ pretreatment (P = .63), anti-EGFR exposure increased TMB (P = .028), whereas lack of anti-EGFR exposure resulted in declining TMB (P = .014).Paired tissue and ctDNA sequencing identified multiple novel mutations, copy gains, and fusions associated with anti-EGFR therapy that frequently co-occur as subclonal alterations in the same patient.
Lung Cancer in Rwanda
Authors: Brandon A. Niyibizi, Eulade Muhizi, Diana A. Ndoli, Ivan Rukundo, Thierry Z. Muvunyi, Maurice Musoni, Damas Dukundane, Emmanuel Rudakemwa, Fidel Rubagumya, Achille Van Christ Manirakiza
Journal: Journal of Thoracic Oncology (2022)
Neonatal outcomes for women at risk of preterm delivery given half dose versus full dose of antenatal betamethasone: a randomised, multicentre, double-blind, placebo-controlled, non-inferiority trial
Authors: Thomas Schmitz, Muriel Doret-Dion, Loic Sentilhes, Olivier Parant, Olivier Claris, Laurent Renesme, Julie Abbal, Aude Girault, Héloïse Torchin, Marie Houllier, Nolwenn Le Saché, Alexandre J Vivanti, Daniele De Luca, Norbert Winer, Cyril Flamant, Claire Thuillier, Pascal Boileau, Julie Blanc, Véronique Brevaut, Pierre-Emmanuel Bouet, Géraldine Gascoin, Gaël Beucher, Valérie Datin-Dorriere, Stéphane Bounan, Pascal Bolot, Christophe Poncelet, Corinne Alberti, Moreno Ursino, Camille Aupiais, Olivier Baud, Philippe Boize, Charles Garabédian, Florence Flamein, Maela Le Lous, Alain Beuchée, Jean Gondry, Pierre Tourneux, Perrine Coste-Mazeau, Antoine Bedu, Denis Gallot, Karen Coste, Céline Chauleur, Hugues Patural, Gilles Kayem, Delphine Mitanchez, Hélène Heckenroth, Farid Boubred, Jeanne Sibiude, Luc Desfrère, Caroline Bohec, Thierry Mansir, Antoine Koch, Pierre Kuhn, Nadia Tillouche, Fabrice Lapeyre, Franck Perrotin, Géraldine Favrais, Edouard Lecarpentier, Xaxier Durrmeyer, Véronique Equy, Thierry Debillon, Luc Rigonnot, Stéphanie Lefoulgoc, Claudia Brie, Anne-Sophie Pagès, Romy Rayssiguier, Gilles Cambonie, Corinne Cudeville, Doriane Madeleneau, Olivier Morel, Jean-Michel Hascoet, Vincent Letouzey, Massimo Di Maio, Laurent J. Salomon, Alexandre Lapillonne
Journal: The Lancet (2022)
Racial Variations in the Prevalence of Primary Open-angle Glaucoma
Authors: James M. Tielsch
Journal: JAMA (1991)

<h3>Objective.</h3> —To compare the prevalence of primary open-angle glaucoma between black and white Americans. <h3>Design, Setting, and Participants.</h3> —The design was a population-based prevalence survey of a noninstitutionalized black and white population aged 40 years or older from the eastern and southeastern health districts of Baltimore, Md. A multistage random sampling strategy was used to identify 7104 eligible participants, of whom 5308 (2395 blacks, 2913 whites) received an ophthalmologic screening examination. Those with abnormalities were referred for definitive diagnostic evaluation. <h3>Main Outcome Measure.</h3> —Primary open-angle glaucoma was defined based on evidence of glaucomatous optic nerve damage, including abnormal visual fields and/or severe optic disc cupping, and was independent of intraocular pressure. <h3>Main Results.</h3> —Age-adjusted prevalence rates for primary open-angle glaucoma were four to five times higher in blacks as compared with whites. Rates among blacks ranged from 1.23% in those aged 40 through 49 years to 11.26% in those 80 years or older, whereas rates for whites ranged from 0.92% to 2.16%, respectively. There was no difference in rates of primary open-angle glaucoma between men and women for either blacks or whites in this population. Based on these data, an estimated 1.6 million persons aged 40 years or older in the United States have primary open-angle glaucoma. <h3>Conclusions.</h3> —Black Americans are at higher risk of primary open-angle glaucoma than their white neighbors. This may reflect an underlying genetic susceptibility to this disease and indicates that additional efforts are needed to identify and treat this sight-threatening disorder in high-risk communities. (<i>JAMA</i>. 1991;266:369-374)
Endoscopic ultrasonography-guided bilateral drainage with antegrade stenting in patient with malignant hilar biliary obstruction after bowel reconstruction
Authors: Ryosuke Sato, Kazuyuki Matsumoto, Hiroyuki Terasawa, Yuki Fujii, Tatsuhiro Yamazaki, Shigeru Horiguchi, Hironari Kato
Journal: Endoscopy (2022)

Endoscopic ultrasonography-guided hepaticogastrostomy (EUS-HGS) and uncovered self-expandable metal stent (SEMS) placement between the right and left intrahepatic bile ducts, called the bridging method, is useful for bilateral drainage in patients with malignant hilar biliary obstruction [1]. Combined EUS-HGS and EUS antegrade stenting is reported to reduce the rate of bile leakage and to prolong stent patency [2]. Access from B2 makes it easier to operate the guidewire downstream of the bile duct than from B3, and the use of a forward-viewing echoendoscope reduces the risk of transesophageal puncture [3].